FUNCTION OF NOVEL GENE (BRG1) EXPRESSED IN PANCREATIC BETA CELLS AND IMPLICATION IN PATHOGENESIS OF DIABETES.

点击翻译按钮获取中文摘要

Complementary DNA of BRG1 (β related gene 1) has been isolated from the mouse pancreatic β cell-line (MIN6) which shows high level of BRG1 expression. In the research theme-1, rabbit polyclonal antibody against synthetic BRG1 peptides was obtained. Using this antibody, we examined the cellular localization of BRG1 protein in the pancreatic islet of mouse model for type 2 diabetes, db/db. Light-microscopic immunofluorescent staining for BRG1 protein revealed the cellular topography in the pancreatic a cells but not β, δ, or PP cells. Other non-endocrine tissues, i.e., liver and kidney, did not show any staining for BRG1 antibody. Immunoelectron microscopy revealed that the co-localization of BRG1 protein in the glucagon-granule in the pancreatic a cells. We assume that the pancreatic β cell line may de-differentiate to express protein which is normally expressed in the pancreatic α cells. BRG1 may be a unique protein which is colocalized in the glucagon granule of pancreatic α cells.In … More the research theme-2 and theme-3, we carried out the genetic analysis of the genes which are etiologically related to diabetes. We obtained the genomic DNA samples from type 1 diabetic patients, GAD antibody-positive or negative type 2 diabetic patients, and normal control subjects. In the research theme-2, we investigated polymorphisms of inhibitor of κB-like (IKBL ; also known as"NFKBIL1") gene which is reported the association to cellular apoptosis and locates in the class III region of HLA complex. The results indicated a possible independent association between type 1 diabetes and SNPs in the promoter of the IKBL gene. In the research theme-3, we conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. The data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes. Less